A Review of Biological Factors Implicated in Abdominal Aortic Aneurysm Rupture

Abstract

Abdominal aortic aneurysm (AAA) rupture is the 13th commonest cause of death in the Western World. Although considerable research has been applied to the aetiology and mechanism of aneurysm expansion, little is known about the mechanism of rupture. Aneurysm rupture was historically considered to be a simple physical process that occurred when the aortic wall could no longer contain the haemodynamic stress of the circulation. However, AAAs do not conform to the law of Laplace and there is growing evidence that aneurysm rupture involves a complex series of biological changes in the aortic wall. This paper reviews the available data on patient variables associated with aneurysm rupture and presents the evidence implicating biological factors in AAA rupture.

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…MMP-14 has been detected in human abdominal aortic aneurysms, which are lesions with the potential to rupture (Choke et al, 2005;Thompson et al, 2002), accompanied by a MMP-14 over-expression (Annabi et al, 2002). Elevated transplantation with bone marrow from MMP-14 null mice resulted in a resistance to aortic aneurysm formation, a finding which supports the importance of MT1-MMP/TIMP-2-driven proMMP-2 activation in aneurysm formation (Xiong et al, 2009).…”

“…The observation clearly suggests that upregulation of stromelysin-1 (MMP-3) and TIMP-3 may play a significant role in aneurysm genesis, but molecular mechanisms are far from being understood. It seems anyway plausible that an excessive production of stromelysin-1 in the atherosclerotic aorta weakens the aortic wall and brings about additional proteolysis by activating other latent, constitutively expressed metalloproteinases (Choke et al, 2005). The origin of this increased stromelysin-1 expression in certain individuals prone to aneurysm formation is not known, but a combination of genetic and environmental factors may contribute (Carrell et al, 2002).…”

“…Aneurysm. In human abdominal aortic aneurysms, which are lesions with the potential to rupture (Choke et al, 2005), MMP-13 is the most expressed MMP (Tromp et al, 2004). Moreover, there are differences in sex for collagen regulation during rodent experimental abdominal aortic aneurysm formation.…”

“…MMP-8 and MMP-13 collagenases are believed to be ultimately responsible for plaque destabilization and rupture as the play physiological role in the control of collagen degradation in blood vessels; conversely, MMP-1 plays a protective role in human atherosclerosis (Galis et al, 1995). In addition, all collagenases seem involved in abdominal aortic aneurysm (AAA), which is characterized by degradation of extracellular matrix, chronic inflammatory cell infiltration and extensive neovascularization (Choke et al, 2005).…”

Inferior STEMI Complicated by Retroperitoneal Hemorrhage due to Ruptured AAA

“…The USPSTF recommends a one-time screening abdominal ultrasound in men between the ages of 65 and 75 who have ever smoked, with a class B recommendation (strong evidence that the effect is moderate, or moderate effect that the evidence is strong) . 10 The prevalence of AAA is estimated to be 1.3% in women and 5-9% in men over 65 11,12 , with mortality due to ruptured AAA as high as 90% 13 , making ruptured AAA the 13 th leading cause of death in the western world as of 2005 14 . Further complicating matters, open AAA repair is associated with a 53% mortality, compared to 24% with endovascular aneurysm repair (EVAR).…”